Study shows lower blood pressure could save lives. How does this finding affect preclinical research?

Jan 22, 2016, 10:28 AM by User Not Found

A recent study1 revealed patients were almost a third less likely to experience heart failure, heart attacks, and strokes when systolic blood pressure was reduced below current guidelines, which usually define ideal systolic pressure as below 140 mm Hg (below 150 mm Hg for people over 60). The NIH-supported study, called SPRINT, randomly assigned 9,361 patients age 50 or older with systolic pressure between 130 to 180 mm Hg and high risk of cardiovascular disease to one of two systolic blood pressure targets: less than 120 mm Hg, or less than 140 mm Hg.

Some cardiologists are now questioning if current blood pressure guidelines are enough. Could lowering systolic pressure targets save lives? Yes, according to SPRINT results, which showed a 27% reduction in mortality in the 120 mm Hg or lower group. But others caution that decreasing pressure too much could lead to adverse effects, including dizziness and kidney failure. Also, the SPRINT results may only apply to those with similar cardiovascular profiles as study participants (although a 2015 meta-analysis2 suggests that lower blood pressure reduces risks regardless of baseline blood pressure and comorbidities).

One point, however, is clear: as clinicians refine standards for optimal blood pressure, precise data are more important than ever for drawing applicable conclusions from research. The same is true for animal models used as proxies for human physiology. Ultimately, SPRINT highlights the need for consistency and measurement accuracy in all research, including preclinical studies.

Direct measurement with implantable telemetry is widely viewed as the best method for detecting subtle changes in blood pressure in preclinical research subjects. Implantable telemetry allows for pressure to be continuously monitored from conscious, freely moving animals without stress artifact.

Safety pharmacology research may be one of the areas most affected by refinement of blood pressure standards. According to ICH guidelines, dedicated cardiovascular tests, including appropriate blood pressure assessments, are necessary before testing pharmaceuticals on humans. As the window of acceptable blood pressure narrows, accurate preclinical measurement is imperative for ensuring unsafe compounds do not move on to clinical trials.

1 The SPRINT Research Group. (2015) “A Randomized Trial of Intensive versus Standard Blood-Pressure Control.” New England Journal of Medicine. 373:2103-2116 DOI: 10.1056/NEJMoa1511939

2 Ettehad, D., Emdin, C. A., Kiran, A., Anderson, S. G., Callender, T., Emberson, J., Chalmers, J., Rodgers, A., Rahimi, K. (2015). “Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis.” The Lancet. 373:2103-2116 DOI: 10.1056/NEJMoa1511939